ABSTRACT
BACKGROUND: In 2017, varicella vaccination became mandatory for all children in Italy, based on a two-dose schedule administered at 12-15 months of age and 5 to 6 years of age. Varicella vaccines are available in different formulations (as a single vaccine or as a combination vaccine together with measles, mumps, and rubella) and are made by multiple manufacturers with different effectiveness profiles. This study calculates the cost-effectiveness of a range of varicella vaccination strategies to identify the optimal strategy for Italy. METHODS: A dynamic transmission cost-effectiveness model was applied in Italy to simulate the long-term (50 years) costs and outcomes associated with different varicella vaccination strategies. Five vaccination strategies were evaluated using the model: two doses of two different combination Measles-Mumps-Rubella-Varicella vaccines (either Vaccine A (MSD) [denoted QQVa] or Vaccine B (GSK) [denoted QQVb]); a first dose of a single Varicella vaccine followed by a second dose of a combination vaccine (either Vaccine C (MSD) followed by Vaccine A [denoted MQVa] or Vaccine D (GSK) followed by Vaccine B [denoted MQVb]); or no vaccine at all (NV). The model was adapted for Italy using publicly available Italian data and expert opinion. RESULTS: Over the 50-year time-horizon, in the absence of universal varicella vaccination, there would be 34.8 million varicella cases, 142 varicella-infection-related deaths, and 23 billion in societal costs. The cost per capita from a societal perspective ranged from 164.55 to 392.18 with NV being the most expensive and QQVa the least expensive. The most effective strategy was QQVa, which resulted in a 66% decrease in varicella cases and 30% reduction in varicella-related deaths compared to NV strategy. QQVa led to a net saving in societal cost around 13 billion compared to NV as the cost of vaccination was more than offset by the savings that resulted from the reduced burden of illness. CONCLUSION: Varicella vaccination has a major impact on reducing varicella incidence, prevalence, and societal costs. This analysis supports the policy for universal varicella vaccination in Italy as the NV strategy was the most expensive and resulted in the poorest outcomes. QQVa offers the greatest benefits at the lowest cost and should be considered as a potential priority strategy for Italian population.
ABSTRACT
In association with their mechanisms of self/non-self recognition (known as mating type systems), ciliates synthesize and constitutively secrete cell type-specific proteins into their extracellular medium. These proteins, designated as pheromones, have been isolated from species of Euplotes and shown to be members of families of structurally homologous molecules, all rich in intra-chain disulfide bonds and organized exclusively in helical conformation. Due to their similar architectures, they can interact with their membrane receptors in competition with one another and bind effectively to their cells of origin in autocrine fashion, or to other co-specific cells in paracrine fashion. In the former case, they promote the vegetative cell growth; in the latter, they induce cells to temporarily arrest their growth stage and shift to a mating (sexual) stage. These varied, context-dependent activities of ciliate pheromones imply an early evolution of basic properties of animal growth factors and cytokines in the unicellular eukaryotes.
Subject(s)
Euplotes/metabolism , Pheromones/metabolism , Pheromones/physiology , Animals , Eukaryotic Cells/physiology , Signal Transduction/physiologyABSTRACT
Homologous proteins, denoted pheromones, promote cell mitotic proliferation and mating pair formation in the ciliate Euplotes raikovi, according to whether they bind to cells in an autocrine- or paracrine-like manner. The primary transcripts of the genes encoding these proteins undergo alternate splicing, which generates at least two distinct mRNAs. One is specific for the soluble pheromone, the other for a pheromone isoform that remains anchored to the cell surface as a type II protein, whose extracellular C-terminal region is structurally equivalent to the secreted form. The 15-kDa membrane-bound isoform of pheromone Er-1, denoted Er-1mem and synthesized by the same E. raikovi cells that secrete Er-1, has been purified from cell membranes by affinity chromatography prepared with matrix-bound Er-1, and its extracellular and cytoplasmic regions have been expressed as recombinant proteins. Using the purified material and these recombinant proteins, it has been shown that Er-1mem has the property of binding pheromones competitively through its extracellular pheromone-like domain and associating reversibly and specifically with a guanine nucleotide-binding protein through its intracellular domain. It has been concluded that the membrane-bound pheromone isoforms of E. raikovi represent the cell effective pheromone binding sites and are functionally equipped for transducing the signal generated by this binding.
